A5060992997- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- Cancer Treatment and Pharmacology
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- Chronic Myeloid Leukemia Treatments
- Angiogenesis and VEGF in Cancer
- Cell death mechanisms and regulation
- DNA Repair Mechanisms
- Neuroblastoma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
Texas Oncology
2009-2025
South Texas Accelerated Research Therapeutics
2015-2024
Sidney Kimmel Comprehensive Cancer Center
2020
Clinical Trials of Texas
2005-2019
Yale Cancer Center
2006-2017
Roswell Park Comprehensive Cancer Center
2017
Theravance Biopharma (United States)
2017
Institut Bergonié
2017
Center for Health Care Services
2013-2017
Start Treatment & Recovery Centers
2012-2015
PURPOSE: To assess the feasibility of administering OSI-774, to recommend a dose on protracted, continuous daily schedule, characterize its pharmacokinetic behavior, and acquire preliminary evidence anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated escalating doses OSI-774 in three study parts (A C) evaluate progressively longer treatment intervals. Part A patients received 25 100 mg once daily, for 3 days each week, weeks every 4 weeks. B...
This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics pharmacodynamics of pembrolizumab in patients with advanced solid tumors.In a 3 + dose escalation study, 10 received 1, 3, or mg/kg intravenously every 2 weeks until progression intolerable toxicity. Seven additional weeks. Thirteen participated 3-week intrapatient (dose range, 0.005-10 mg/kg) followed by Tumor response was assessed Response Evaluation Criteria Solid Tumors (RECIST)...
We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor cyclin-dependent kinases (CDK) 4 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, colorectal cancer. A total 225 patients were enrolled: 33 192 cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated 200...
AKT signaling is frequently deregulated in human cancers. MK-2206 a potent, oral allosteric inhibitor of all isoforms with antitumor activity preclinical models. A phase I study was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary efficacy.Patients advanced solid tumors received on alternate days. Paired tumor biopsies were mandated at the MTD for biomarker studies. PD studies incorporated hair follicle...
This study evaluated the clinical relevance of dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways.We investigated safety, efficacy, correlations between tumor genetic alterations benefit in 236 patients with advanced cancers treated phase I drugs targeting phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways our Phase Clinical Trials Program.Seventy-six (32.2%) received a PI3K pathway inhibitor combination MAPK (D), whereas 124...
Significance CALAA-01 is a targeted nanoparticle containing siRNA that first-in-class experimental therapeutic for cancer. To our knowledge, it the first targeted, polymer-based nanoparticle-carrying to be systemically administered humans. Results from human phase Ia/Ib clinical trial are presented and correlated preclinical animal data provide an initial assessment of how this class therapeutics translated animals
Ulixertinib (BVD-523) is an ERK1/2 kinase inhibitor with potent preclinical activity in BRAF- and RAS-mutant cell lines. In this multicenter phase I trial (NCT01781429), 135 patients were enrolled to accelerated 3 + dose-escalation cohort six distinct dose-expansion cohorts. Dose escalation included 27 patients, dosed from 10 900 mg twice daily established the recommended II dose (RP2D) of 600 daily. exposure was proportional RP2D, which provided near-complete inhibition ERK whole blood....
To assess the feasibility of administering XRP6258, a new taxane with low affinity for multidrug resistance 1 protein, as 1-hour i.v. infusion every 3 weeks. The study also sought to determine maximum tolerated dose and recommended dose, describe pharmacokinetic (PK) behavior compound, seek preliminary evidence anticancer activity.Twenty-five patients advanced solid malignancies were treated 102 courses XRP6258 at four levels ranging from 10 25 mg/m(2). Dose escalation was based on...
Purpose To assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity mapatumumab (HGS-ETR1, TRM-1), a fully human agonist monoclonal antibody directed to tumor necrosis factor–related apoptosis-inducing ligand receptor-1 (TRAIL-R1). Patients Methods with advanced solid malignancies were treated escalating doses intravenously (IV) administered over 30 120 minutes, initially as single dose then repetitively. Plasma concentrations measured serum was assayed detect...
To determine the maximum-tolerated dose (MTD) and to assess safety, pharmacokinetics, evidence of antitumor activity AMG 479, a fully human monoclonal antibody insulin-like growth factor receptor 1 (IGF-1R).Patients with advanced solid malignancies or non-Hodgkin's lymphoma received escalating doses 479 intravenously (IV) every 2 weeks (Q2W). Blood samples were assayed pharmacokinetic parameters IGF-1R occupancy on neutrophils; fluorodeoxyglucose-positron emission tomography scans used tumor...
To determine the maximum-tolerated dose (MTD) and assess safety, pharmacokinetics, pharmacodynamics, evidence of antitumor activity RO4929097, a gamma secretase inhibitor Notch signaling in patients with advanced solid malignancies.Patients received escalating doses RO4929097 orally on two schedules: (A) 3 consecutive days per week for 2 weeks every weeks; (B) 7 weeks. reversible CYP3A4 autoinduction, expanded part study tested three dosing as above; modified A, d/wk (C) continuous daily...
Purpose Ridaforolimus is an inhibitor of mammalian target rapamycin, integral component the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess antitumor ridaforolimus patients distinct subtypes advanced Patients and Methods metastatic or unresectable soft tissue bone sarcomas received 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks....
To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL).Phase I dose-escalation study including NHL, cohort type 2 diabetes mellitus. Patients received three weekly intravenous infusions copanlisib per 28-day cycle over range 0.1-1.2 mg/kg. Plasma levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS,...
Triple-negative breast cancer (TNBC) is characterized by the absence of expression estrogen receptor, progesterone and HER-2. Thirty percent patients recur after first-line treatment, metastatic TNBC (mTNBC) has a poor prognosis with median survival one year. Here, we present initial analyses whole genome transcriptome sequencing data from 14 prospective mTNBC. We have cataloged collection somatic genomic alterations in these advanced tumors, particularly those that may inform targeted...
Abstract Purpose: This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist T-cell costimulatory receptor 4-1BB/CD137 in combination with humanized, PD-1–blocking IgG4 pembrolizumab patients advanced solid tumors. Experimental Design: Utomilumab (0.45–5.0 mg/kg) (2 were administered intravenously every 3 weeks. dose escalation was conducted using time-to-event continual reassessment method....
Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is investigational, fully human CSF1R antibody that inhibits binding ligands and IL34 subsequent ligand-mediated activation. This first-in-human phase I study evaluated safety, pharmacokinetics, pharmacodynamics, antitumor activity 820.Experimental Design: Adult patients with...
Background Availability of checkpoint inhibitors has created a paradigm shift in the management patients with solid tumors. Despite this, most do not respond to immunotherapy, and there is considerable interest developing combination therapies improve response rates outcomes. B7-H3 (CD276) member B7 family cell surface molecules provides an alternative immune molecule therapeutically target alone or programmed death-1 (PD-1)–targeted therapies. Enoblituzumab, investigational anti-B7-H3...
This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC).
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to potent, exatecan-derived topoisomerase I inhibitor payload via plasma-stable, selectively cleavable linker.
Abstract Purpose: Eganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming Immuno-Oncology-1 (NCT02637531) study evaluated the safety tolerability of once-daily eganelisib as monotherapy nivolumab patients solid tumors. Patients Methods: Dose-escalation cohorts...
Temozolomide, an oral DNA methylator that inactivates the repair enzyme O(6)-alkylguanine-DNA alkyltransferase (AGAT), has demonstrated anticancer activity on protracted schedules. Protracted schedules may lead to 'autoenhancement' of temozolomide's inherent cytotoxic potential by cumulative reduction cell's capacity for AGAT-mediated and resistance. This study was undertaken characterise AGAT inactivation regeneration in peripheral blood mononuclear cells (PBMCs) patients treated two...
This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies.Patients were treated using an accelerated titration design sequential escalating flat doses administered 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QDx5) 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, tumor...